Neurometabolic disorders are caused by problems of the brain to con vertone metabolite in to another , caused by a shortage in the enzyme responsible for this chemical reaction. This conversion problem results in accumulation of metabolites and/or reduced levels of other metabolites. Such an imbalance in metabolite levels can affect development and function of the brain and the central nervous system, and patients will present with neurological symptoms at a very young age. If therapy is possible, this should be started as early as possible to prevent damage to the patient. In the metabolic laboratory, several methods are available to investigate which meta bolites are not in balance. However, it has not been possible so far to investigate all metabolites at the same time. We have now developed a new method that is able to analyze 10,000 metabolites at the same time , which we have named ‘next generation metab olic screening ’ (NGMS). In this project, we want to use this new method to analyze cerebrospinal fluid of patients with the neurometabolic disorders tyrosine hydroxylase deficiency and pyridoxine - dependent epilepsy . By analyzing all possible metabolites, we want to show that our new method can diagnose these diseases, but can also find novel biomarkers. For the future, we also inte nd to use this method to iden tify novel biomarkers for yet uncharacterized disorders. We believe that patients will benefit great ly from a correct diagnosis. It will allow the physician to start the optimal treatment as soon as possible, but will also give patients and their family closure of their diagnostic search.